I. Field of the Invention
Embodiments are directed generally to medicine, immunology, and microbiology. In particular embodiments are directed to malaria vaccines.
II. Description of Related Art
Malaria is a mosquito-borne infectious disease of humans and other animals caused by parasitic protozoans of the Plasmodium type. Most deaths are caused by P. falciparum with P. vivax, P. ovale, and P. malariae generally causing milder forms of malaria. Malaria causes symptoms that include fever, fatigue, vomiting, and headaches. In severe cases it can cause yellow skin, seizures, coma, or death. These symptoms usually begin ten to fifteen days after being bitten by a mosquito carrying plasmodium. For subjects who have recently survived an infection, re-infection typically causes milder symptoms.
Natural clinical immunity to malaria develops slowly, is only temporary in the absence of repeated natural infection, and is strain-specific. The immune correlates of protection are only partially understood, but have long been known to involve antibodies to blood stage forms of the parasite (Cohen et al., Nature, 192:733-737, 1961; Sabchareon et al., Am J Trop Med Hyg, 45(3):297-308, 1991). A number of proteins are implicated in Plasmodium faliciparum's ability to target and enter erythrocytes. However, many of these proteins are highly polymorphic, making development of a vaccine effective across different strains of P. falciparum challenging. A recent study of ten different proteins present on malarial blood-stage parasites showed that the protein called reticulocyte-binding protein homolog 5 (or Rh5) was the most effective at eliciting neutralizing antibodies (Douglas et al., Nat Commun, 2:601, 2011). RH5 is one of the essential proteins involved in merozoite invasion of erythrocytes and has a lower level of polymorphism among strains compared to other malaria vaccine targets (Baum et al., Int J Parasital, 39(3):371-380, 2009; Chen et al., PLoS Pathog, 7(9):e1002199, 2011). Remarkably, a recent study indicated that sera from individuals in a holoendemic malaria region of Africa show very “minimal acquisition” of anti-Rh5 antibodies (Williams et al., PLoS Pathog, 8(11):e1002991, 2012). This suggests that despite its promise as a vaccine antigen, RH5 is not particularly immunogenic during natural malaria infection. Nevertheless, it has recently been shown that although they are not very abundant, anti-RH5 antibodies present in infected individuals can inhibit parasite invasion of red blood cells, in vitro (Patel et al., J Infect Dis, 2013). Taken together, these data reflect the opportunity for an RH5-based vaccine to provide effective cross strain protection in humans. Therefore, RH5 is being pursued as a good target for future vaccine development against P. falciparum. 
There remains a need for additional compositions and methods for prevention and treatment of malaria.